Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Neoplasms

Rare Diseases

Uterine Cervical Diseases

Uterine Cervical Neoplasms

Uterine Cervical Dysplasia

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Coagulants

Vitamins

Acetic Acid

Retinol acetate

Iodine

Lugol's solution

Cadexomer iodine

Swede score colposcopy: includes application with acetic acid, supplemented with a systematic scoring system (the Swede score) including Lugols iodine, and collection of cervical biopsies.

Conventional colposcopy: includes application with acetic acid and collection of cervical biopsies.

New colposcopy method: with application of acetic acid, supplemented with a systematic scoringsystem (Swede score) including Lugols iodine, and collection of cervical biopsies.

Swede score colposcopy

Ane-Kersti Knudsen, MD,Ph.d.stud

Rikke Guldberg

Anne Hammer

Helene Nortvig

Christina Blach

Lone Kjeld Petersen

Eva Hauge

Attila Botházi

Anne Hammer, MD, as.prof

Ulrik Schiøler Kesmodel, MD, prof

Berit Bargum Booth, MD, Ph.d.

Line Winther Gustafson, MD, Ph.d.

Cervical cancer screening is important as it enables identification of women at increased risk of the disease, but high-quality diagnostics of screen-positive women and effective treatment of those with precancer are critical in preventing progression to cancer. With the current transition from cytology-based to primary human papillomavirus (HPV)-screening and a growing proportion of HPV-vaccinated women, diagnostics of screen-positive women will become more challenging in the decades to come. Thus, there is a need to explore how to improve diagnostics while ensuring a low number of unnecessary procedures such as colposcopy and the collection of multiple cervical biopsies.

The overall purpose is:

* To investigate the diagnostic accuracy of cervical precancer when using a colposcopic scoring system in the diagnostic work-up of screen-positive women.
* To investigate the performance of a colposcopic scoring system to identify women without cervical precancer in whom collection of biopsies can be safely omitted.

Introduction Cervical cancer is the fourth most common cancer in women worldwide. Every year, 375 women are diagnosed with cervical cancer in Denmark, and approximately 90 women die from the disease. Cervical cancer is caused by the sexually transmitted virus, human papillomavirus (HPV). When infected about 85-90 % clear the virus within a year or two. The remaining women develop a persistent HPV infection, which is associated with an increased risk of cervical intraepithelial neoplasia (CIN), which may progress to cancer if left untreated. Cervical cancer can be prevented through prophylactic HPV vaccination and screening. In Denmark, women aged 23 - 64 years are invited to the screening program. Women who do not participate in regular screening have an increased risk of cervical cancer, however up to 55% of cervical cancers are diagnosed in women who have attended screening. Hence, the performance of diagnostics is crucial.

Diagnostics Women with abnormal screening results may undergo repeat testing or be referred for colposcopy. Colposcopy allows the colposcopist to magnify and visualize the cervix with the transformation zone, where cervical cancer and cervical lesions typically arise. The aim is to make a colposcopic diagnosis and select the most severe area for biopsies, which undergo histopathological examination. Studies have shown considerable inter- and intra-observer variability even among experienced colposcopists, and a variable sensitivity of colposcopy as low as 55-57%. These findings suggest a need to improve the detection rate of CIN2+. A validated colposcopic scoring system, the Swede score, has been designed to improve the detection of high-grade cervical lesions, specified as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by providing an systematic approach to the colposcopy examination. The Swede score includes five variables (degree of 1) acetowhitening, 2) margins and surface, 3) vessels, 4) lesion size, and 5) iodine staining by using Lugols iodine) with a score from 0 - 2. Conventional colposcopy only utilizes acetic acid. In the original study, the Swede score had a high sensitivity and specificity for detecting high-grade cervical lesions (CIN2+), with an area under the receiver operating characteristics (ROC) curve of 0.87. Even so, the Swede score is endorsed by the International Agency for Research on Cancer (IARC/WHO) and by the European Federation for Colposcopy (EFC), it has not yet been implemented in Denmark. As previous studies have mostly evaluated the use of the Swede score among expert colposcopists, it is important to assess whether the score may be a valuable tool among non-experts. In Denmark, colposcopy is mostly performed by non-experts gynecologists. As a result of the low performance of colposcopy, and because several studies have shown that the CIN2+ detection rate increases with the number of biopsies collected, the Danish national guidelines recommend that all women should have a minimum of 4 biopsies collected. Biopsies should be collected from abnormal areas of the cervix and, if no lesion is detected, random biopsies should be taken. Our neighboring Scandinavian countries, for example Sweden and Finland, do not recommend collection of random biopsies. If biopsies could be omitted without increasing the risk of missing disease and reducing the harms with pain, bleeding and discomfort, this would benefit the women.

Aim The project aims to explore whether the implementation of a systematic colposcopic scoring system, the Swede score, can improve diagnostic accuracy of cervical lesions with detection of CIN2+ in a Danish clinical setting. Furthermore, we want to evaluate whether the Swede score can be used to assess when random biopsies can be safely omitted.

Data Characteristics of the women will be collected from medical records (previous gynecological historic, parity, smoking status, HPV-vaccination status, hormone use or immunosuppressive treatment). From the Danish Pathology Databank, we will collect data on previous screening history, result of the referral screening test, result of current and subsequent cervical biopsies and/or cervical excision.

This study is focused on cervical cancer and precancer. Since only women have a cervix, only women will be included in this study.

iMproving thE DIagnostics And Treatment Of ceRvical Precancer

The number of women diagnosed with Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) diagnosed in cervical biopsies

University of Aarhus

Infections

Symptoms and General Pathology

Communicable Diseases

Papillomavirus Infections

Disease Attributes

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Vaccines

The subject who is receiving first or second dose of the AS04 adjuvanted HPV 16/18 vaccine at the enrollment.

The subject who does not have any HPV vaccination history at the enrollment or during the study period.

A brief questionnaire will be administered to all participants at enrollment and at the pre-scheduled follow-up visit at Month 36.

For the subject who are eligible for the screening (i.e. (1)≥ 18 years old; (2) had sexual debut prior to enrollment, (3) no contradiction to the screening, (4) voluntary to the screening) will be referred to the study site hospitals by offering the subjects a cervical cancer screening voucher, and the type-specific HPV test will be performed as primary screening approach at Month 0 and 36.

Questionnaire Survey and Cervical Cancer Screening

Take AS04 adjuvanted HPV16/18 vaccine as an example to evaluate the impact of HPV vaccination on HPV infection and related disease burden in the real world based on prospective cohort and Yinzhou Regional Health Information Platform (YRHIP), in order to bridge the gap in relevant evidence in China.

Impact of HPV Vaccination on HPV Infection and Cervical Related Disease Burden in Real-World Settings (HPV-RWS)

Impact of HPV Vaccination on HPV Infection and Cervical Related Disease Burden in Real-World Settings (HPV-RWS): A Prospective Cohort

HPV-16 and/or HPV-18 infection is defined as at least one positive HPV-16 or HPV-18 DNA PCR assay at enrollment (Month 0) or follow-up (Month 36) or any additional screenings during the study period.

12 other hr-HPV positive besides of type 16/18 infection is defined as at least one positive for HPV 31/33/35/39/45/51/52/56/58/59/66/68 or multiple types DNA PCR assay at enrollment (Month 0) or follow-up (Month 36) or any additional screenings during the study period.

Any cervical lesions or diseases is defined as atypical squamous cells of undefined significance (ASC-US), atypical glandular cells (AGC), atypical squamous cells, cannot exclude for highly squamous intraepithelial lesions (ASC-H), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), Cervical Intraepithelial Neoplasia (CIN) 1, CIN2, CIN3, squamous cell carcinoma (SCC), adenocarcinoma in situ (AIS) and adenocarcinoma (ADC). Any hr-HPV type infection is defined as at least one positive for HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 or multiple types DNA PCR assay in the aforesaid cervical sample.

Center for Disease Control and Prevention of Yinzhou District, Ningbo City, China

GlaxoSmithKline

Peking University

Women referred to colposcopy at our facilities who met inclusion criteria

Women who have a colposcopy exam performed at Randers Regional Hospital were examined by Dynamic Spectral Imaging colposcopy (DYSIS)

Dynamic Spectral Imaging (DYSIS)

Berit B Booth, MD

Berit B Booth

Christina B Kristensen, MD

Pinar Bor, MD, PhD

Lone K Petersen, MD, Med.Sc.D.

Jan Blaakaer, MD, Med.Sc.D.

Katja Dahl, MD, PhD

This study evaluates the Dynamic Spectral Imaging (DSI) Colposcope (DySIS) in it's ability to diagnose cervical dysplasia. Half of participants with be examined by the DySIS colposcope, there the other half will be examined by standard colposcopy.

Colposcopy has been shown to be a subjective exam, and is dependant on the colposcopists. Sensitivity for colposcopy has been shown to be as low as 50%.

To improve this, different adjunctive technologies have been introduced to add a more objective approach to the colposcopy exam. One of these devices is the DySIS colposcope, which measures the aceto-white reaction that may occur on the cervix uteri after the application of acetic-acid. The device provides the examiner with a colour-coded map indicating areas of interest. Studies have shown promising results indicating that using this device together with the colposcopists own interpretation of the cervix uteri can potentially lead to an increase in the performance of the colposcopy exam.

In Denmark all women referred for colposcopy have 4 biopsies taken, according to the Danish national guidelines.

In our study these 4 biopsies are as following:

1. The area the colposcopists views as the worst before the DSI-map is seen. Colposcopy-Directed Biopsy (CDB)
2. The area indicated as the worst by the DSI-map (DSI-directed biopsy)
3. additional biopsy
4. additional biopsy All biopsies are placed in separate containers and analysed separately by specialized pathologists.

Colposcopy and Dynamic Spectral Imaging (DSI)

Does Dynamic Spectral Imaging (DSI) Colposcopy Improve the Diagnostics of Cervical Dysplasia Compared to Standard Colposcopy

The proportion of women who are found with a histological CIN2+ diagnosis in the cervical punch biopsy from the area chosen by the colposcopist before the DSI-map became visible (will be referred to as the Colposcopy directed biopsy (CDB)).

The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

The proportion of women who are found with a histological CIN2+ diagnosis in cervical punch biopsy taken from the worst area indicated by the DSI-map (referred to as the DSI-directed biopsy) The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

The amount of women who are found with a histological CIN2+ diagnosis in cervical punch biopsies taken from 2 additional areas besides the CDB and the DSI-directed areas.

The diagnosis of the biopsy will be recorded when the histological report is available.

Further treatment needs for the patient will be based on the national clinical guidelines on cervical dysplasia.

Comparing the histological diagnosis of the cervical punch biopsies to the cone biopsy, in women who are referred for conization based on the histological outcome of the colposcopy procedure.

Immune System Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

HIV Seropositivity

Central Nervous System Depressants

Anti-Arrhythmia Agents

Channel Blockers

Anesthetics

Lidocaine

Anesthetics, Local

those who serologically tested positive for HIV

those who serologically tested negative for HIV

those with no available serological test for HIV

Cervical specimen obtained using speculum examination and cervical collection bush.

Screening

Vaginal speculum examination followed by application of 2% acetic acid and lugol's iodine with inspection with colposcope and punch biopsies taken of abnormal areas.

Colposcopy

The above (see colposcopy) is followed by local anaesthetic with two dentist's ampoules of lignocaine and large loop excision using coagulation of the abnormal area (usually 2 x 3 x 1 cm).

LLETZ

Greta Dreyer, PhD

Cathy Visser, MSc

Leon C Snyman, MMedO&G;FCOG

Greta D Dreyer, PhD

Nearly 8 000 new cervical cancer cases are diagnosed in South Africa per year; many are still undiagnosed and about 50% of diagnosed cases succumb per year. Although the current prevalence of pre-cancer cervical disease is largely unknown, data from local studies suggest regional differences and an increase in the prevalence of cytological abnormalities when compared with historical data. Low frequency in cytology screening is the primary factor attributable to development of invasive cervical cancer and almost one-third of all cervical cancer patients had previous negative cytology. Due to the low sensitivity of cytology it can be assumed that the true prevalence of pre-cancer disease is underestimated by all available data. One round of optimal cervical cytology will detect around 50% of existing pre-cancer cervical disease as identified and proven using colposcopy and directed biopsy. It is now widely accepted that primary screening with a human papilloma virus (HPV) test can improve the sensitivity of screening and that even a single round of HPV screening can rapidly reduce the incidence of invasive cervical cancer and related mortality within a few years.

South Africa has a high prevalence of HIV infection and a delay in or failure to initiate antiretroviral therapy (ART). These facts, together with the largely unscreened status of the female population and the high incidence of cervical cancer all suggest that HPV infection and precursors to cervical cancer are both unusually common among South African women. Accurate current knowledge of the performance of newer generation HPV based screening tests in HIV-infected and general female population are essential for cost-analysis and planning for national prevention and screening programs. This study will aim to demonstrate the feasibility and efficacy of new generation HPV deoxyribonucleic acid (DNA) based screening assays in a South African setting.

The investigators hypothesize that HPV testing followed by normal and special cytology tests will be a successful screening model for a South African population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
iMproving thE DIagnostics And Treatment Of ceRvical Precancer	NCT05870787	Cervical Dyspla... Cervical Diseas... Cervical Lesion Cervical Cancer Cervical Neopla...	Swede score col...	23 Years - 99 Years	University of Aarhus
Impact of HPV Vaccination on HPV Infection and Cervical Related Disease Burden in Real-World Settings (HPV-RWS)	NCT05341284	HPV Infection Cervical Diseas...	Questionnaire S...	9 Years - 45 Years	Peking University
Colposcopy and Dynamic Spectral Imaging (DSI)	NCT04249856	Cervical Dyspla... Cervical Diseas... Cervical Lesion Cervix Cancer Cervical Cancer Cervical Neopla...	Dynamic Spectra...	18 Years -	University of Aarhus
Screening Study for Cervical Pre-cancer and Cancer Prevention in South African Women.	NCT02956031	Cervical Cancer High Grade Sil CIN2	Screening Colposcopy LLETZ	25 Years - 75 Years	University of Pretoria

Spots Global Cancer Trial Database for cervical disease